Listeria monocytogenes is a food-borne pathogen that primarily afflicts immunocompromised individuals and can provoke septicaemia, meningitis and fetal infection or abortion in infected pregnant women.
L. monocytogenes is an excellent model for intracellular infection, as it mediates its own uptake into non-phagocytic cells, subsequently escapes from the vacuole, polymerizes actin to spread from cell to cell and secretes factors that alter transcription, post-translational modifications, innate immune signalling and cytoskeletal rearrangements.
L. monocytogenes can traverse three distinct epithelial barriers and competes for a niche in the dense intestinal microbiota through upregulation of metabolic pathways and the secretion of toxic bactericidal factors.
L. monocytogenes utilizes a plethora of complex regulation strategies such as riboregulators and small non-coding RNAs to quickly adapt to and thrive in highly divergent physiological contexts.
Listeria monocytogenes is a food-borne pathogen responsible for a disease called listeriosis, which is potentially lethal in immunocompromised individuals. This bacterium, first used as a model to study cell-mediated immunity, has emerged over the past 20 years as a paradigm in infection biology, cell biology and fundamental microbiology. In this Review, we highlight recent advances in the understanding of human listeriosis and L. monocytogenes biology. We describe unsuspected modes of hijacking host cell biology, ranging from changes in organelle morphology to direct effects on host transcription via a new class of bacterial effectors called nucleomodulins. We then discuss advances in understanding infection in vivo, including the discovery of tissue-specific virulence factors and the 'arms race' among bacteria competing for a niche in the microbiota. Finally, we describe the complexity of bacterial regulation and physiology, incorporating new insights into the mechanisms of action of a series of riboregulators that are critical for efficient metabolic regulation, antibiotic resistance and interspecies competition.
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Murray, E. G. D., Webb, M. A. & Swann, M. B. R. A. Disease of rabbits characterised by a large mononuclear leucocytosis, caused by a hitherto undescribed bacillus Bacterium monocytogenes (n.sp.). J. Pathol. 29, 407–439 (1926).
Schlech W. F. III, Lavigne P. M., Bortolussi, R. A., Allen A. C., Haldane, E. V. et al. Epidemic listeriosis — evidence for transmission by food. N. Engl. J. Med. 308, 203–206 (1983).
de Noordhout, C. M. et al. The global burden of listeriosis: a systematic review and meta-analysis. Lancet Infect. Dis. 14, 1073–1082 (2014).
McLauchlin, J. Human listeriosis in Britain, 1967–1985, a summary of 722 cases. 1. Listeriosis during pregnancy and in the newborn. Epidemiol. Infect. 104, 181–189 (1990).
McLauchlin, J. Human listeriosis in Britain, 1967–1985, a summary of 722 cases. 2. Listeriosis in non-pregnant individuals, a changing pattern of infection and seasonal incidence. Epidemiol. Infect. 104, 191–201 (1990).
Weller, D., Andrus, A., Wiedmann, M. & den Bakker, H. C. Listeria booriae sp. nov. and Listeria newyorkensis sp. nov., from food processing environments in the USA. Int. J. Syst. Evol. Microbiol. 65, 286–292 (2015).
Gandhi, M. & Chikindas, M. L. Listeria: A foodborne pathogen that knows how to survive. Int. J. Food Microbiol. 113, 1–15 (2007).
Tasara, T. & Stephan, R. Cold stress tolerance of Listeria monocytogenes: a review of molecular adaptive mechanisms and food safety implications. J. Food Prot. 69, 1473–1484 (2006).
de las Heras, A., Cain, R. J., Bielecka, M. K. & Vazquez-Boland, J. A. Regulation of Listeria virulence: PrfA master and commander. Curr. Opin. Microbiol. 14, 118–127 (2011).
Cossart, P. Illuminating the landscape of host–pathogen interactions with the bacterium Listeria monocytogenes. Proc. Natl Acad. Sci. USA 108, 19484–19491 (2011).
Bakardjiev, A. I., Theriot, J. A. & Portnoy, D. A. Listeria monocytogenes traffics from maternal organs to the placenta and back. PLoS Pathog. 2, e66 (2006).
Pizarro-Cerdá, J., Kühbacher, A. & Cossart, P. Entry of Listeria monocytogenes in mammalian epithelial cells: an updated view. Cold Spring Harbor Persp. Med. 2, a010009 (2012).
Lambrechts, A., Gevaert, K., Cossart, P., Vandekerckhove, J. & Van Troys, M. Listeria comet tails: the actin-based motility machinery at work. Trends Cell Biol. 18, 220–227 (2008).
Bierne, H. & Cossart, P. When bacteria target the nucleus: the emerging family of nucleomodulins. Cell. Microbiol. 14, 622–633 (2012).
Cossart, P. & Helenius, A. Endocytosis of viruses and bacteria. Cold Spring Harbor Persp. Biol. 6, a016972 (2014).
Bierne, H., Sabet, C., Personnic, N. & Cossart, P. Internalins: a complex family of leucine-rich repeat-containing proteins in Listeria monocytogenes. Microbes Infect. 9, 1156–1166 (2007).
Sabet, C., Lecuit, M., Cabanes, D., Cossart, P. & Bierne, H. LPXTG protein InlJ, a newly identified internalin involved in Listeria monocytogenes virulence. Infect. Immun. 73, 6912–6922 (2005).
Kühbacher, A. et al. Genome-wide siRNA screen identifies complementary signaling pathways involved in Listeria infection and reveals different actin nucleation mechanisms during Listeria cell invasion and actin comet tail formation. mBio 6, e00598-15 (2015).
Agaisse, H. et al. Genome-wide RNAi screen for host factors required for intracellular bacterial infection. Science 309, 1248–1251 (2005).
Kirchner, M. & Higgins, D. E. Inhibition of ROCK activity allows InlF-mediated invasion and increased virulence of Listeria monocytogenes. Mol. Microbiol. 68, 749–767 (2008).
Perelman, S. S. et al. Cell-based screen identifies human interferon-stimulated regulators of Listeria monocytogenes infection. PLoS Pathog. 12, e1006102 (2016).
Xayarath, B., Alonzo, F. 3rd & Freitag, N. E. Identification of a peptide-pheromone that enhances Listeria monocytogenes escape from host cell vacuoles. PLoS Pathog. 11, e1004707 (2015).
Rabinovich, L., Sigal, N., Borovok, I., Nir-Paz, R. & Herskovits, A. A. Prophage excision activates Listeria competence genes that promote phagosomal escape and virulence. Cell 150, 792–802 (2012).
Feiner, R. et al. A new perspective on lysogeny: prophages as active regulatory switches of bacteria. Nat. Rev. Microbiol. 13, 641–650 (2015).
Birmingham, C. L. et al. Listeriolysin O allows Listeria monocytogenes replication in macrophage vacuoles. Nature 451, 350–354 (2008).
Lam, G. Y., Cemma, M., Muise, A. M., Higgins, D. E. & Brumell, J. H. Host and bacterial factors that regulate LC3 recruitment to Listeria monocytogenes during the early stages of macrophage infection. Autophagy 9, 985–995 (2013).
Nikitas, G. et al. Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin. J. Exp. Med. 208, 2263–2277 (2011). This study highlights the role of L. monocytogenes transcytosis of goblet cells for intestinal epithelial barrier crossing.
Hamon, M. A., Ribet, D., Stavru, F. & Cossart, P. Listeriolysin O: the Swiss army knife of Listeria. Trends Microbiol. 20, 360–368 (2012).
Stavru, F., Bouillaud, F., Sartori, A., Ricquier, D. & Cossart, P. Listeria monocytogenes transiently alters mitochondrial dynamics during infection. Proc. Natl Acad. Sci. USA 108, 3612–3617 (2011).
Stavru, F., Palmer, A. E., Wang, C. X., Youle, R. J. & Cossart, P. Atypical mitochondrial fission upon bacterial infection. Proc. Natl Acad. Sci. USA 110, 16003–16008 (2013). This work reveals an atypical Drp1-independent mitochondrial fission provoked by bacterial infection that requires the ER membrane to physically constrict mitochondria and actin polymerization.
Pillich, H., Loose, M., Zimmer, K. P. & Chakraborty, T. Activation of the unfolded protein response by Listeria monocytogenes. Cell. Microbiol. 14, 949–964 (2012).
Kaser, A. et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134, 743–756 (2008).
Malet, J. K., Cossart, P. & Ribet, D. Alteration of epithelial cell lysosomal integrity induced by bacterial cholesterol-dependent cytolysins. Cell. Microbiol. 19, e12682 (2017).
Lebreton, A. et al. A bacterial protein targets the BAHD1 Chromatin complex to stimulate type III interferon response. Science 331, 1319–1321 (2011). This paper identifies LntA, the first in a class of L. monocytogenes virulence factors called nucleomodulins, which sequesters the transcriptional repressor BAHD1, thereby activating genes induced by type III interferon.
Lebreton, A. et al. Structural basis for the inhibition of the chromatin repressor BAHD1 by the bacterial nucleomodulin LntA. mBio 5, e00775-13 (2014).
Lebreton, A. et al. A direct interaction between the bacterial nucleomodulin LntA and the chromatin repressor BAHD1 modulates interferon responses to infection. FEBS J. 281, 726–727 (2014).
Radoshevich, L. & Dussurget, O. Cytosolic innate immune sensing and signaling upon infection. Front. Microbiol. 7, 313 (2016).
Dussurget, O., Bierne, H. & Cossart, P. The bacterial pathogen Listeria monocytogenes and the interferon family: type I, type II and type III interferons. Front. Cell. Infect. Microbiol. 4, 50 (2014).
Theisen, E. & Sauer, J. D. Listeria monocytogenes and the inflammasome: from cytosolic bacteriolysis to tumor immunotherapy. Curr. Top. Microbiol. Immunol. 397, 133–160 (2016).
Hamon, M. A. et al. Histone modifications induced by a family of bacterial toxins. Proc. Natl Acad. Sci. USA 104, 13467–13472 (2007).
Hamon, M. A. & Cossart, P. K+ efflux is required for histone H3 dephosphorylation by Listeria monocytogenes listeriolysin O and other pore-forming toxins. Infection Immun. 79, 2839–2846 (2011).
Eskandarian, H. A. et al. A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science 341, 1238858 (2013). This study identifies a previously unknown nuclear role for SIRT2 in deacetylation of H3K18, which is downstream of InlB–Met receptor signalling and is required for effective infection.
Samba-Louaka, A., Stavru, F. & Cossart, P. Role for telomerase in Listeria monocytogenes infection. Infect. Immun. 80, 4257–4263 (2012).
Samba-Louaka, A. et al. Listeria monocytogenes dampens the DNA damage response. PLoS Pathog. 10, e1004470 (2014).
Leitao, E. et al. Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection. Cell Cycle 13, 928–940 (2014).
Veiga, E. & Cossart, P. Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nat. Cell Biol. 7, 894–900 (2005). This study demonstrates that large cargoes such as bacteria could be internalized by using the clathrin-dependent endocytic machinery.
Bonazzi, M., Veiga, E., Pizarro-Cerda, J. & Cossart, P. Successive post-translational modifications of E-cadherin are required for InlA-mediated internalization of Listeria monocytogenes. Cell. Microbiol. 10, 2208–2222 (2008).
Bonazzi, M. et al. Clathrin phosphorylation is required for actin recruitment at sites of bacterial adhesion and internalization. J. Cell Biol. 195, 525–536 (2011).
Bonazzi, M. et al. A common clathrin-mediated machinery co-ordinates cell-cell adhesion and bacterial internalization. Traffic 13, 1653–1666 (2012).
Ribet, D. et al. Listeria monocytogenes impairs SUMOylation for efficient infection. Nature 464, 1192–1195 (2010).
Impens, F., Radoshevich, L., Cossart, P. & Ribet, D. Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. Proc. Natl Acad. Sci. USA 111, 12432–12437 (2014).
Ribet, D. et al. Promyelocytic leukemia protein (PML) controls Listeria monocytogenes infection. mBio 8, e02179-16 (2017).
Boujemaa-Paterski, R. et al. Listeria protein ActA mimics WASP family proteins: it activates filament barbed end branching by Arp2/3 complex. Biochemistry 40, 11390–11404 (2001).
Jasnin, M. et al. Three-dimensional architecture of actin filaments in Listeria monocytogenes comet tails. Proc. Natl Acad. Sci. USA 110, 20521–20526 (2013).
Truong, D., Copeland, J. W. & Brumell, J. H. Bacterial subversion of host cytoskeletal machinery: hijacking formins and the Arp2/3 complex. Bioessays 36, 687–696 (2014).
Fattouh, R. et al. The diaphanous-related Formins promote protrusion formation and cell-to-cell spread of Listeria monocytogenes. J. Infect. Dis. 211, 1185–1195 (2015).
Rigano, L. A., Dowd, G. C., Wang, Y. & Ireton, K. Listeria monocytogenes antagonizes the human GTPase Cdc42 to promote bacterial spread. Cell. Microbiol. 16, 1068–1079 (2014).
Rajabian, T. et al. The bacterial virulence factor InlC perturbs apical cell junctions and promotes cell-to-cell spread of Listeria. Nat. Cell Biol. 11, 1212–1218 (2009). This work reveals that the L. monocytogenes virulence factor InlC alters cell rigidity in order to facilitate bacterial cell-to-cell spread.
Czuczman, M. A. et al. Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread. Nature 509, 230–234 (2014). This paper highlights the involvement of efferocytosis in the recipient cell during cell-to-cell spread.
Auerbuch, V., Brockstedt, D. G., Meyer-Morse, N., O'Riordan, M. & Portnoy, D. A. Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J. Exp. Med. 200, 527–533 (2004).
Carrero, J. A., Calderon, B. & Unanue, E. R. Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection. J. Exp. Med. 200, 535–540 (2004).
O'Connell, R. M. et al. Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J. Exp. Med. 200, 437–445 (2004).
Stockinger, S. et al. IFN regulatory factor 3-dependent induction of type I IFNs by intracellular bacteria is mediated by a TLR- and Nod2-independent mechanism. J. Immunol. 173, 7416–7425 (2004).
Osborne, S. E. et al. Type I interferon promotes cell-to-cell spread of Listeria monocytogenes. Cell. Microbiol. 19, e12660 (2017).
Gutierrez, M. G. et al. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119, 753–766 (2004).
Yoshikawa, Y. et al. Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nat. Cell Biol. 11, 1233–1240 (2009). This paper identifies the importance of ActA-mediated autophagy evasion during L. monocytogenes infection.
Mostowy, S. et al. p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways. J. Biol. Chem. 286, 26987–26995 (2011).
Mitchell, G. et al. Avoidance of autophagy mediated by PlcA or ActA is required for Listeria monocytogenes growth in macrophages. Infect. Immun. 83, 2175–2184 (2015).
Lecuit, M. et al. A single amino acid in E-cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes. EMBO J. 18, 3956–3963 (1999).
Lecuit, M. et al. A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier. Science 292, 1722–1725 (2001).
Pentecost, M., Kumaran, J., Ghosh, P. & Amieva, M. R. Listeria monocytogenes Internalin B activates junctional endocytosis to accelerate intestinal invasion. PLoS Pathog. 6, e1000900 (2010).
Gessain, G. et al. PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes. J. Exp. Med. 212, 165–183 (2015).
Khelef, N., Lecuit, M., Bierne, H. & Cossart, P. Species specificity of the Listeria monocytogenes InlB protein. Cell. Microbiol. 8, 457–470 (2006).
Wollert, T., Heinz, D. W. & Schubert, W. D. Thermodynamically reengineering the listerial invasion complex InlA/E-cadherin. Proc. Natl Acad. Sci. USA 104, 13960–13965 (2007).
Wollert, T. et al. Extending the host range of Listeria monocytogenes by rational protein design. Cell 129, 891–902 (2007).
Tsai, Y. H., Disson, O., Bierne, H. & Lecuit, M. Murinization of Internalin extends its receptor repertoire, altering Listeria monocytogenes cell tropism and host responses. PLoS Pathog. 9, e1003381 (2013).
Jones, G. S. et al. Intracellular Listeria monocytogenes comprises a minimal but vital fraction of the intestinal burden following foodborne infection. Infect. Immun. 83, 3146–3156 (2015).
Jones, G. S. & D'Orazio, S. E. Monocytes are the predominant cell type associated with Listeria monocytogenes in the gut, but they do not serve as an intracellular growth niche. J. Immunol. 198, 2796–2804 (2017).
Bleriot, C. et al. Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection. Immunity 42, 145–158 (2015).
Charlier, C. et al. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. Lancet Infect. Dis. 17, 510–519 (2017).
Bakardjiev, A. I., Stacy, B. A. & Portnoy, D. A. Growth of Listeria monocytogenes in the guinea pig placenta and role of cell-to-cell spread in fetal infection. J. Infect. Dis. 191, 1889–1897 (2005).
Disson, O. et al. Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis. Nature 455, 1114–1118 (2008). This study identifies key determinants required to cross the placental barrier.
Lecuit, M. et al. Targeting and crossing of the human maternofetal barrier by Listeria monocytogenes: role of internalin interaction with trophoblast E-cadherin. Proc. Natl Acad. Sci. USA 101, 6152–6157 (2004).
Zeldovich, V. B., Robbins, J. R., Kapidzic, M., Lauer, P. & Bakardjiev, A. I. Invasive extravillous trophoblasts restrict intracellular growth and spread of Listeria monocytogenes. PLoS Pathog. 7, e1002005 (2011).
Zeldovich, V. B. et al. Placental syncytium forms a biophysical barrier against pathogen invasion. PLoS Pathog. 9, e1003821 (2013).
Faralla, C. et al. InlP, a new virulence factor with strong placental tropism. Infect. Immun. 84, 3584–3596 (2016).
Rolhion, N. & Chassaing, B. When pathogenic bacteria meet the intestinal microbiota. Philos. Trans. R. Soc. Lond. B Biol. Sci. 371, 20150504 (2016).
Archambaud, C. et al. Impact of lactobacilli on orally acquired listeriosis. Proc. Natl Acad. Sci. USA 109, 16684–16689 (2012).
Archambaud, C. et al. The intestinal microbiota interferes with the microRNA response upon oral Listeria infection. mBio 4, e00707-13 (2013).
Becattini, S. et al. Commensal microbes provide first line defense against Listeria monocytogenes infection. J. Exp. Med. 214, 1973–1989 (2017). This study dissects the relative contributions of the microbiota and the immune response in listeriosis and identifies four strains of bacteria that have antibacterial properties against L. monocytogenes.
Becavin, C. et al. Comparison of widely used Listeria monocytogenes strains EGD, 10403S, and EGD-e highlights genomic variations underlying differences in pathogenicity. mBio 5, e00969-14 (2014).
Cotter, P. D. et al. Listeriolysin S, a novel peptide haemolysin associated with a subset of lineage I Listeria monocytogenes. PLoS Pathog. 4, e1000144 (2008).
Quereda, J. J. et al. Bacteriocin from epidemic Listeria strains alters the host intestinal microbiota to favor infection. Proc. Natl Acad. Sci. USA 113, 5706–5711 (2016). This study identifies the first bacteriocin-like virulence factor in L. monocytogenes.
Dussurget, O. et al. Listeria monocytogenes bile salt hydrolase is a PrfA-regulated virulence factor involved in the intestinal and hepatic phases of listeriosis. Mol. Microbiol. 45, 1095–1106 (2002).
Begley, M., Sleator, R. D., Gahan, C. G. & Hill, C. Contribution of three bile-associated loci, bsh, pva, and btlB, to gastrointestinal persistence and bile tolerance of Listeria monocytogenes. Infect. Immun. 73, 894–904 (2005).
Dowd, G. C., Joyce, S. A., Hill, C. & Gahan, C. G. Investigation of the mechanisms by which Listeria monocytogenes grows in porcine gallbladder bile. Infect. Immun. 79, 369–379 (2011).
Toledo-Arana, A. et al. The Listeria transcriptional landscape from saprophytism to virulence. Nature 459, 950–956 (2009).
Mraheil, M. A. et al. The intracellular sRNA transcriptome of Listeria monocytogenes during growth in macrophages. Nucleic Acids Res. 39, 4235–4248 (2011).
Wurtzel, O. et al. Comparative transcriptomics of pathogenic and non-pathogenic Listeria species. Mol. Syst. Biol. 8, 583 (2012).
Dar, D. et al. Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria. Science 352, aad9822 (2016). This fascinating paper identifies new L. monocytogenes riboregulators, one of which is critical for antibiotic resistance.
Lebreton, A. & Cossart, P. RNA- and protein-mediated control of Listeria monocytogenes virulence gene expression. RNA Biol. 14, 460–470 (2016).
Reniere, M. L. et al. Glutathione activates virulence gene expression of an intracellular pathogen. Nature 517, 170–173 (2015).
Hall, M. et al. Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria. Proc. Natl Acad. Sci. USA 113, 14733–14738 (2016).
Mandin, P. et al. VirR, a response regulator critical for Listeria monocytogenes virulence. Mol. Microbiol. 57, 1367–1380 (2005).
Kang, J., Wiedmann, M., Boor, K. J. & Bergholz, T. M. VirR-mediated resistance of Listeria monocytogenes against food antimicrobials and cross-protection induced by exposure to organic acid salts. Appl. Environ. Microbiol. 81, 4553–4562 (2015).
Abachin, E. et al. Formation of D-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes. Mol. Microbiol. 43, 1–14 (2002).
Thedieck, K. et al. The MprF protein is required for lysinylation of phospholipids in listerial membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on Listeria monocytogenes. Mol. Microbiol. 62, 1325–1339 (2006).
Behrens, S. et al. Ultra deep sequencing of Listeria monocytogenes sRNA transcriptome revealed new antisense RNAs. PloS ONE 9, e83979 (2014).
Burke, T. P. et al. Listeria monocytogenes is resistant to lysozyme through the regulation, not the acquisition, of cell wall-modifying enzymes. J. Bacteriol. 196, 3756–3767 (2014).
Boneca, I. G. et al. A critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system. Proc. Natl Acad. Sci. USA 104, 997–1002 (2007).
Burke, T. P. & Portnoy, D. A. SpoVG is a conserved RNA-binding protein that regulates Listeria monocytogenes lysozyme resistance, virulence, and swarming motility. mBio 7, e00240-16 (2016).
Quereda, J. J., Ortega, A. D., Pucciarelli, M. G. & Garcia-del Portillo, F. The Listeria small RNA Rli27 regulates a cell wall protein inside eukaryotic cells by targeting a long 5′-UTR variant. PLoS Genet. 10, e1004765 (2014).
Mellin, J. R. et al. A riboswitch-regulated antisense RNA in Listeria monocytogenes. Proc. Natl Acad. Sci. USA 110, 13132–13137 (2013).
Mellin, J. R. et al. Sequestration of a two-component response regulator by a riboswitch-regulated noncoding RNA. Science 345, 940–943 (2014). This study identifies a two-component system that can be sequestered by a riboswitch-regulated RNA in L. monocytogenes.
Aubry, C. et al. OatA, a peptidoglycan O-acetyltransferase involved in Listeria monocytogenes immune escape, is critical for virulence. J. Infect. Dis. 204, 731–740 (2011).
Pensinger, D. A. et al. The Listeria monocytogenes PASTA kinase PrkA and its substrate YvcK are required for cell wall homeostasis, metabolism, and virulence. PLoS Pathog. 12, e1006001 (2016).
Marles-Wright, J. et al. Molecular architecture of the “stressosome,” a signal integration and transduction hub. Science 322, 92–96 (2008).
Impens, F. et al. N-terminomics identifies Prli42 as a membrane miniprotein conserved in Firmicutes and critical for stressosome activation in Listeria monocytogenes. Nat. Microbiol. 2, 17005 (2017). This study maps the translational landscape of L. monocytogenes through a proteomics approach, thus identifying a small protein that interacts with the stressosome and affects stress signalling.
Orsi, R. H. & Wiedmann, M. Characteristics and distribution of Listeria spp., including Listeria species newly described since 2009. Appl. Microbiol. Biotechnol. 100, 5273–5287 (2016).
Maury, M. M. et al. Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity. Nat. Genet. 48, 308–313 (2016).
Moura, A. et al. Whole genome-based population biology and epidemiological surveillance of Listeria monocytogenes. Nat. Microbiol. 2, 16185 (2016).
Ragon, M. et al. A new perspective on Listeria monocytogenes evolution. PLoS Pathog. 4, e1000146 (2008).
Abdullah, Z. et al. RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids. EMBO J. 31, 4153–4164 (2012).
Hagmann, C. A. et al. RIG-I detects triphosphorylated RNA of Listeria monocytogenes during Infection in non-immune cells. PloS ONE 8, e62872 (2013).
Radoshevich, L. et al. ISG15 counteracts Listeria monocytogenes infection. eLife 4, e06848 (2015). This paper reveals an early interferon-independent induction of ISG15 in non-phagocytic cells as well as an anti-listerial function of ISGylation, which was previously thought to be primarily antiviral.
Woodward, J. J., Iavarone, A. T. & Portnoy, D. A. c-Di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science 328, 1703–1705 (2010). This seminal paper discovers that a bacterial cyclic dinucleotide can directly activate STING to upregulate type I interferon.
Archer, K. A., Durack, J. & Portnoy, D. A. STING-dependent type I IFN production inhibits cell-mediated immunity to Listeria monocytogenes. PLoS Pathog. 10, e1003861 (2014). This paper explores the idea that L. monocytogenes secretes cyclic di-AMP because early activation of innate immune signalling has a deleterious effect on T cell-mediated immunity following subsequent exposure.
McFarland, A. P. et al. Sensing of bacterial cyclic dinucleotides by the oxidoreductase RECON promotes NF-κB activation and shapes a proinflammatory antibacterial state. Immunity 46, 433–445 (2017).
Ribet, D. & Cossart, P. How bacterial pathogens colonize their hosts and invade deeper tissues. Microbes Infect. 17, 173–183 (2015).
Quereda, J. J. & Cossart, P. Regulating bacterial virulence with RNA. Annu. Rev. Microbiol. 71, 263–280 (2017).
The authors apologize to those colleagues whose work could not be included owing to space constraints. The authors gratefully acknowledge financial support from the European Research Area Network (ERA-NET) Infect-ERA BACVIRISG15 and PROANTILIS, the European Research Council (ERC) Advanced Grant BacCellEpi (670823), Agence Nationale de la Recherche (ANR) BACNET (10-BINF-02-01), ANR Investissement d'Avenir Programme (10-LABX-62-IBEID), Human Frontier Science Program (HFSP; RGP001/2013), the Balzan Foundation, the Pasteur-Weizmann Council and the Fondation le Roch les Mousquetaires. The authors thank D. Ribet, J.J. Quereda, S. Brisse and M. Lecuit for allowing us to adapt their figures. The authors thank H. Bierne, J. Pizarro-Cérda and O. Dussurget for helpful discussions. L.R. is supported by an HFSP long-term fellowship. P.C. is a senior international research scholar of the Howard Hughes Medical Institute, USA.
The authors declare no competing financial interests.
- Actin nucleation
The assembly of monomeric actin into filaments by actin nucleators, which can result in branched or linear actin filaments depending on the actin nucleator.
- Actin-based motility
Listeria monocytogenes-mediated motility co-opts cellular actin nucleators to form bundles of actin that propel the bacterium within the cell and allow it to spread from one cell to another.
- Receptor-mediated endocytosis
Cellular uptake of host surface receptors to regulate growth factor signalling or receptor turnover; the process requires monoubiquitylation of the receptor, clathrin and actin.
A Listeria monocytogenes protein characterized by leucine-rich repeat domains that can be anchored to the bacterial cell wall by a sorting motif or secreted.
- Vacuolar rupture
Vacuolar damage (or phagosomal damage in phagocytic cells) by bacterial virulence factors that allow bacterial escape into the cytosol.
- Phage excision
The active process of removal of DNA from a lysogenic (non-lytic) bacteriophage that was previously integrated into the bacterial genome.
- LC3-mediated phagocytosis
Phagocytosis in which the autophagy microtubule-associated protein light-chain 3 (LC3) is conjugated to the lipid phosphatidylethanolamine on the inside of the plasma membrane.
- Mitochondrial fission
Mitochondrial division mediated by dedicated cellular factors called dynamin-related protein 1 (DRP1 and mitochondrial fission factor (Mff).
- Unfolded protein response
(UPR.) When the protein folding demand of the endoplasmic reticulum (ER) exceeds its capacity, this response upregulates chaperones, blocks translation into the ER and increases ER folding capacity.
A class of proteases that degrade other proteins and are typically activated by the acidic conditions in the lysosome.
A class of bacterial virulence factors that are expressed in the cytoplasm and travel to the nucleus where they can affect host transcription.
- Bromo adjacent homology domain-containing 1 protein
(BAHD1). A protein that is part of a transcriptional repression complex that affects the expression of interferon-stimulated genes following Listeria monocytogenes infection.
A protein that is important in endocytosis and exocytosis and has heavy chain variants and light chain variants that form a polyhedral lattice on the surface of vesicles.
The process by which a small ubiquitin-like modifier covalently binds to its substrates. This typically leads to changes in localization or sequestration of transcription factors resulting in transcriptional repression.
A family of proteins that polymerize actin; each formin can have distinct actin-nucleating properties depending on the family.
- Diaphanous formins
A subset of formins that have an autoinhibitory domain that is released by binding to GTPases.
The process for phagocytosing dead or dying cells that is initiated by the recognition of phosphatidylserine lipids on the cell surface (lipids normally present on the internal side of the plasma membrane).
A catabolic process that can nonspecifically or selectively capture cytosolic contents, organelles or invading pathogens and target them for degradation in the lysosome.
A programmed cell death process, distinct from apoptosis, which generates inflammatory signals and typically occurs during infection.
Cells that will form the placenta, which are derived from fetal tissue and form the external layer of the developing blastocyst in the context of pregnancy.
A condition in which the precise contents of the microbiota (bacteria and other microorganisms) of an animal are known; can refer to zero bacteria (germ-free) or a known subset of bacteria.
- Immune priming
Transcriptional activation of innate defence pathways or immune memory pathways that leads to a subsequent downstream immune response that is more pronounced than the initial naive immune response.
- ANTAR element
An RNA-binding domain called AmiR and NasR transcriptional anti-terminator regulator (ANTAR).
- Attenuation-like mechanism
A mechanism of transcriptional control in bacteria and archaea that incorporates a terminator sequence into the 5′ mRNA leader that can stall the ribosome (resulting in aborted translation) or allow readthrough depending on metabolic conditions.
- Ribosomal stalling
An event that occurs when the ribosome slows during translation, often owing to a specific secondary structure in the mRNA, resulting in aborted translation or temporary ribosomal pausing.
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Radoshevich, L., Cossart, P. Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis. Nat Rev Microbiol 16, 32–46 (2018). https://doi.org/10.1038/nrmicro.2017.126
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